DM

Question 1

define excess alcohol intake (M+F)

Answer 1

> 30g/d for M, >20g/d for F

Question 2

_% Western population have fatty liver?

Answer 2

30%

Question 3

What symptoms can occur in NAFLD pts?

Answer 3

RUQ discomfort w/ tenderness on palpation, fatigue, and hepatomegaly

Question 4

list some LFTs

Answer 4

ALT, GGT, Alk phos (+imaging)

Question 5

metabolic syndrome is comprised of…

Answer 5

obesity, insulin resistance, T2DM, hypertension, low HDL, high tryglycerides

Question 6

causes of NAFLD

Answer 6

metabolic disease, HCV, surgical complications, drugs/toxins, coeliac disease, genetics, rapid weight alteration

Question 7

how does HCV precipitate NAFLD?

Answer 7

alteration of glucose and lipid metabolism allows for accumulation of fat in liver

Question 8

describe the spectrum of disease in NAFLD

Answer 8

steatosis -> steatohepatitis (^ inflam and collagen deposition) -> fibrosis -> liver cirrhosis (irreversible) -> HCC

Question 9

a Dx of NASH requires what 3 things?

Answer 9

steatosis, lobular/portal inflammation, and ballooning

Question 10

How does insulin signalling impact the development of steatosis?

Answer 10

^lipolysis of triacylglycerols (TAG) and release of fatty acids from adipocytes caused by insulin signalling results in more fatty aids being delivered to liver + increased hepatic glucose delivery + ^gluconeogenesis and decreasing glycogen synthesis > new lipolysis

Question 11

insulin resistance is thought to be caused by…

Answer 11

protein kinase C-epsilon phosphorylating insulin receptor threonine kinase, thus suppressing signalling

Question 12

how does dysbiosis cause steatosis?

Answer 12

low-Q, kcal-dense diets cause unwanted changes in gut microbiota > damage integrity of epithelial lining through ^production of SCFA, ethanol, metabolites. epithelial damage > permeability > circulationof damaging biproducts -> liver

Question 13

sources of oxidative stress

Answer 13

mitochondrial dysfunction, peroxisomes, microsomes, ER, plasma membrane, cytoplasm

Question 14

how does ER stress cause oxidative stress?

Answer 14

more food consumed > more insulin to make > overworked endoplasmic reticulum > dysfunction

Question 15

Oxidative stress via reduction in antioxidants

Answer 15

v.synthesis/inhibition of antioxidant enzymes, or depletion of Low molecular mass direct antioxidants (through diet?)

Question 16

give an example of antioxidant enzyme inhibition

Answer 16

antioxidant transcription factor Nfr2, triggered to produce antioxidants as adaptive response to O* stress, can trigger harmful inflam processes and apoptosis if prolonged

Question 17

insulin signalling and ROS

Answer 17

insulin signalling stims ROS productino by NAPDH oxidases on ER and plasma membrane, which become converted to H2O2, and also inactivates antioxidant enzymes like peroxidase1. ^H2O2, in return, oxidises and inactivates protein tyrosine phosphatase enzymes, allowing insulin-r signalling to proceed.

Question 18

rare diseases that could be 2ndry causes of liver steatosis

Answer 18

thyroid-related, PCOS, Wilson’s, AI-conditions affected liver or metabolic function

Question 19

Mx options for NAFLD/NASH

Answer 19

diet, exercise, bariatric surgery, drugs: SGLT2i, GLP1 agonists, anti-obesogenic, PPAR-agonists, FXR ligands, THR-blockers

Question 20

types of bariatric surgery

Answer 20

adjustable gastric band, gastric bypass, vertical sleeve gastrectomy

Question 21

BMI >? req for bariatric surgery

Answer 21

BMI >40

Question 22

describe the Mediterranean diet

Answer 22

high in fruits and veggies, legumes, grains, fish and unsaturated fats.

Question 23

why should fructose be avoided?

Answer 23

contribute to overload of ROS through breakdown products and activation of NOX

Question 24

what WL is suggested for NAFLD Mx?

Answer 24

7% or above of total BW

Question 25

describe the production of insulin in beta cells

Answer 25

mRNA > pre-proinsulin in rER > proinsulin in golgi apparatus - cleaved of its C-chain by prohormone convertase 1/3 > insulin + C-peptide in insulin vesicles

Question 26

K-ATP channel is __ at low BG, maintaining __ plasma membrane. Change in BG __ the threshold of __mM causes the channel to __, __-ing the channel and triggering insulin secretion

Answer 26

open, hyperpolarised, above, 5.5, close, depolarising

Question 27

what channels on beta cells do glucose stimulate? What does this activate?

Answer 27

GLUT1/2, production of ATP by mitochondria

Question 28

How does GLUT1/2 activate mitchondrial production of ATP?

Answer 28

^ pyruvate via GCK

Question 29

What does an increase in ATP do in regards to K+-ATP channels?

Answer 29

inhibits K-ATP channels > depolarised membrane > calcium influx > drives insulin release

Question 30

Which DM Mx inhibits K-ATP channels in order to release insulin from beta cells?

Answer 30

sulphonylureas (SU)

Question 31

List some key diabetes Mx

Answer 31

insulin injections, GLP1 agonists, DPP4i, SUs, SGLT2i, metformin

Question 32

how does leptin act on ARC neurons?

Answer 32

excites POMC/CART neurons and inhibits NPY/AgRP neurons, thus promoting the anabolic pathway in PVN

Question 33

how does insulin act on ARC neurons?

Answer 33

excites POMC/CART neurons and inhibits NPY/AgRP neurons, thus promoting the anabolic pathway in PVN

Question 34

how does ghrelin act on ARC neurons?

Answer 34

excites NPY/AgRP neurons and inhibits POMC/CART neurons, thus promoting the catabolic pathway in PVN

Question 35

Where (primarily) are each of leptin, insulin, and ghrelin produced?

Answer 35

leptin: adipose, insulin: pancreatic beta cells, ghrelin: endocrine cells lining stomach and s-intestine

Question 36

What are the 3 key tyrosine groups on the intracellular domain of LEP-Rb?

Answer 36

Y985, Y1077, Y1138

Question 37

Which tyrosine group on LEP-Rb provides a docking site for STAT3 when phosphorylated?

Answer 37

pY1138